Persistent inhibition of FLIPL expression by lentiviral small hairpin RNA delivery restores death-receptor-induced apoptosis in neuroblastoma cells

被引：22

作者：

Flahaut, M ^{[1
]}

Mühlethaler-Mottet, A ^{[1
]}

Auderset, K ^{[1
]}

Bourloud, KB ^{[1
]}

Meier, R ^{[1
]}

Popovic, MB ^{[1
]}

Joseph, JM ^{[1
]}

Gross, N ^{[1
]}

机构：

[1] CHU Vaudois, Dept Paediat, Hematooncol Unit, CH-1011 Lausanne, Switzerland

来源：

APOPTOSIS | 2006年 / 11卷 / 02期

关键词：

apoptosis; death receptors; FLIP; lentivirus-mediated shRNA; neuroblastoma;

D O I：

10.1007/s10495-006-3435-9

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Neuroblastoma represents the most common and deadly solid tumour of childhood, which disparate biological and clinical behaviour can be explained by differential regulation of apoptosis. To understand mechanisms underlying death resistance in neuroblastoma cells, we developed small hairpin of RNA produced by lentiviral vectors as tools to selectively interfere with FLIPL, a major negative regulator of death receptor-induced apoptosis. Such tools revealed highly efficient in interfering with FLIPL expression and function as they almost completely repressed endogenous and/or exogenously overexpressed FLIPL protein and fully reversed FLIPL-mediated TRAIL resistance. Moreover, interference with endogenous FLIPL and FLIPS significantly restored FasL sensitivity in SH-EP neuroblastoma cell line. These results reveal the ability of lentivirus-mediated shRNAs to specifically and persistently interfere with FLIP expression and support involvement of FLIP in the regulation of death receptor-mediated apoptosis in neuroblastoma cells. Combining such tools with other therapeutic modalities may improve treatment of resistant tumours such as neuroblastoma.

引用

页码：255 / 263

页数：9

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